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Reduction in percent of Ki67 positive cells at surgery compared to baseline as a function of treatment. Analysis of the primary treatment comparison will be based on a two sample t-test comparing change in log-transformed Ki67% for placebo and treated subjects. P-values of 0.05 will be considered significant. Proliferation will be assessed by immunohistochemical (IHC) staining for Ki67, and the change in percentage of Ki67 positive cells will be compared in lapatinib-treated samples versus placebo.

Incidence of Adverse Events Graded According to the National Cancer Institute (NCI) Common Terminology Criteria (CTCAE) Version 3.0 [ Time Frame: From baseline to 4-5 weeks after surgery ]

Toxicity profile summarized reflects incidence by number of participants affected with adverse events by Maximum Grade 1 to 3, additional adverse event according to the NCI CTCAE version 3.0 reported in Adverse Event section results.

Incidence of Ductal Carcinoma in Situ Remaining at Resection [ Time Frame: 2-6 weeks from baseline to surgery, up to 6 weeks ]

Number of participants with DCIS incidence on surgical excision. Differences in histologic response (disappearance of DCIS) will be evaluated using Fisher's exact test. Correlation analysis and linear models will be used to evaluate associations among marker values at baseline and among changes in marker values and treatment. All statistical tests will be two-sided.

Biomarker Analysis of Proliferation Markers [ Time Frame: 2-6 weeks from baseline to surgery, Up to 6 weeks ]

Correlation analysis and linear models will be used to evaluate associations among marker values at baseline and among changes in marker values and treatment. All statistical tests will be two-sided.

Neoadjuvant Trial of Lapatinib for the Treatment of Women With DCIS Breast Cancer

Brief Summary

This randomized phase I/II trial studies the side effects and best dose of lapatinib ditosylate and to see how well it works in treating patients with ductal breast carcinoma in situ. Lapatinib ditosylate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Detailed Description

PRIMARY OBJECTIVES:

I. Determine whether lapatinib (lapatinib ditosylate) therapy at the dose of 1000 mg results in a statistically significantly lower rate of proliferation in ductal carcinoma in situ (DCIS) breast cancer cells as measured by Ki67 when compared to placebo.

Participants must have a diagnosis of ductal carcinoma in situ made by core needle biopsy

The DCIS cells must have high expression of human epidermal growth factor receptor 2 (erbB2) (3+ by immunohistochemical staining or amplification by fluorescence in situ hybridization [FISH]), and/or have detectable expression of epidermal growth factor receptor (EGFR) (1+ or more by immunohistochemical staining)

All participants must be informed of the investigational nature of this study and must sign and give written informed consent in accordance with institutional and federal guidelines

Individuals with a diagnosis of breast cancer, non-melanoma skin cancer, cervical cancer in situ, or early bladder cancer are eligible if they have not been treated with chemotherapy, biological therapy, or breast radiotherapy to the breast currently affected by DCIS within one year; in addition, individuals with a diagnosis of breast cancer may not have used tamoxifen, raloxifene, or other antiestrogen compounds within three months of study day 1

If subjects are of reproductive potential, they must agree to use a reliable contraceptive method or be sexually abstinent; subjects must fulfill these conditions beginning at the time of starting study medications and ending one month after study termination

Cardiac ejection fraction within normal limits for the institution by multi gated acquisition scan (MUGA) scan or normal cardiac ultrasound (defined as within the upper limit of normal [ULN] for the institution)

Eastern Cooperative Oncology Group (ECOG) performance status =< 2

Willingness to refrain from donating blood to others during the study

Exclusion Criteria:

Individuals are ineligible if they have either active cancer or a prior history of malignancies other than (e.g., breast cancer, skin cancer [basal or squamous cell carcinoma], cervical cancer in situ, or early bladder cancer [preinvasive transitional cell carcinoma of the bladder]) within the past five years

Participants are ineligible if they are currently being treated with tamoxifen, raloxifene, or with aromatase inhibitors (letrozole, anastrozole, exemestane)

Individuals are ineligible if they have received chemotherapy, biological therapy (e.g., Herceptin), or radiotherapy for the treatment of any cancer within 1 year or if they have received tamoxifen, raloxifene, letrozole, anastrozole, or exemestane therapy within 3 months of study day 1